朊病毒蛋白的正常构象：从天然状态到感染性颗粒。
Normal modes of prion proteins: from native to infectious particle.
机构信息
Department of Structural Biology, Stanford University, Stanford, California 94305, United States.
出版信息
Biochemistry. 2011 Mar 29;50(12):2243-8. doi: 10.1021/bi1010514. Epub 2011 Mar 4.
Abstract
Prion proteins (PrP) are the infectious agent in transmissible spongiform encephalopathies (i.e., mad cow disease). To be infectious, prion proteins must undergo a conformational change involving a decrease in α-helical content along with an increase in β-strand content. This conformational change was evaluated by means of elastic normal modes. Elastic normal modes show a diminution of two α-helices by one and two residues, as well as an extension of two β-strands by three residues each, which could instigate the conformational change. The conformational change occurs in a region that is compatible with immunological studies, and it is observed more frequently in mutant prions that are prone to conversion than in wild-type prions because of differences in their starting structures, which are amplified through normal modes. These findings are valuable for our comprehension of the conversion mechanism associated with the conformational change in prion proteins.
摘要
朊病毒蛋白（PrP）是传染性海绵状脑病（即疯牛病）的感染因子。为了具有传染性，朊病毒蛋白必须经历构象变化，涉及α-螺旋含量的降低以及β-折叠含量的增加。这种构象变化通过弹性正则模态来评估。弹性正则模态显示两个α-螺旋减少一个和两个残基，以及两个β-折叠每个延伸三个残基，这可能引发构象变化。构象变化发生在与免疫研究相容的区域，并且在更易于转换的突变朊病毒中比在野生型朊病毒中更频繁地观察到，这是由于它们的起始结构的差异，这些差异通过正则模态放大。这些发现对于我们理解与朊病毒蛋白构象变化相关的转换机制很有价值。
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